Participation of the E3-ligase TRIM13 in NF-κB p65 activation and NFAT-dependent activation of c-Rel upon T-cell receptor engagement.

Participation of the E3-ligase TRIM13 in NF-κB p65 activation and NFAT-dependent activation of c-Rel upon T-cell receptor engagement.
Int J Biochem Cell Biol. 2014 Jul 31;
Authors: Hatchi EM, Poalas K, Cordeiro N, N'Debi M, Gavard J, Bidère N
Abstract
The nuclear factor κB (NF-κB) family members p65 and c-Rel chiefly orchestrate lymphocytes activation following T-cell receptor (TCR) engagement. In contrast to p65, which is rapidly mobilized, c-Rel activation occurs subsequently as it involves a nuclear factor of activated T-cells (NFAT)-dependent upregulation step. However, how TCR ligation drives p65 and c-Rel activation is not fully understood. Because several ubiquitylated components of NF-κB signaling cascade accumulate in close proximity to membranes, we screened a siRNA library against E3-ligases that contain transmembrane domains on TCR-mediated NF-κB activation. Here, we report the identification of the endoplasmic reticulum resident TRIM13 protein as an enhancer of NF-κB promoter activity. We found that knocking down TRIM13 by RNA interference reduced the activation of p65, while the translocation of c-Rel into the nucleus was blunted. We further observed that c-Rel induction was diminished without TRIM13, as NFAT activation was compromised. These results unveil that TRIM13 is a selective regulator of p65 and of c-Rel activation.
PMID: 25088585 [PubMed - as supplied by publisher]

Source: The International Journal of Biochemistry and Cell Biology - July 31, 2014 Category: Biochemistry Authors: Hatchi EM, Poalas K, Cordeiro N, N'Debi M, Gavard J, Bidère N Tags: Int J Biochem Cell Biol Source Type: research